Back to Encyclopedia

Semax

Cognitive

Also known as: ACTH(4-7)-PGP, Heptapeptide Semax

Half-life: ~2-3 minutes (very rapid degradation; biological effects last hours due to downstream gene expression changes)

CognitiveNeuroprotection

Overview

Semax is a synthetic heptapeptide derived from the adrenocorticotropic hormone (ACTH) fragment ACTH(4-10), with a Pro-Gly-Pro tripeptide extension at the C-terminus for enhanced metabolic stability. Developed in Russia, it was designed to retain the neurotrophic and nootropic properties of ACTH while eliminating the hormonal (steroidogenic) activity. The resulting peptide demonstrates potent neuroprotective effects, enhancing cognitive function, memory formation, and attention without affecting cortisol or adrenal steroid levels.

One of the most significant mechanisms of Semax involves the upregulation of brain-derived neurotrophic factor (BDNF) and its receptor TrkB, which are critical for neuronal survival, synaptic plasticity, and long-term memory consolidation. Semax also modulates the expression of nerve growth factor (NGF) and other neurotrophins, contributing to its broad neuroprotective profile. Additionally, it influences the serotonergic and dopaminergic systems, which may underlie its reported anxiolytic and antidepressant properties.

In Russia, Semax has been used clinically for nearly three decades in the treatment of stroke, transient ischemic attacks, cognitive disorders, and optic nerve atrophy. It is typically administered intranasally, which allows rapid absorption and CNS penetration. Despite its extensive clinical history in Russian medicine, Semax has not been evaluated in Western regulatory frameworks, and most of the published research originates from Russian scientific institutions.

History

Semax was developed in the late 1980s at the Institute of Molecular Genetics of the Russian Academy of Sciences, in the same laboratory that later produced Selank. It was created by Professor Nikolai Myasoedov and colleagues by modifying the ACTH(4-10) fragment with a Pro-Gly-Pro C-terminal extension for metabolic stability. Semax was approved in Russia in 1996 as a treatment for stroke, transient ischemic attacks, cognitive disorders, and optic nerve atrophy. It is also approved in Ukraine. The peptide has been used clinically in Russian medicine for nearly three decades, with extensive post-marketing experience. It was listed in the Russian Pharmacopoeia and is manufactured by several Russian pharmaceutical companies.

Effects

  • Upregulates BDNF and NGF expression for neuroprotection
  • Enhances memory formation, learning, and attention
  • Promotes neuronal survival after ischemic injury
  • Modulates serotonergic and dopaminergic neurotransmission
  • Supports optic nerve health and visual function

Side Effects

  • Mild nasal irritation with intranasal administration
  • Occasional headache
  • Rare anecdotal reports of hair thinning at high doses
  • Mild dizziness in sensitive individuals

Tolerability

Semax has an excellent tolerability profile based on nearly 30 years of clinical use in Russia. The most common side effect is mild nasal irritation with intranasal administration. Headaches are uncommon. Anecdotal reports of hair loss at high doses exist but are rare and typically reversible. The peptide does not affect corticosteroid levels despite being derived from ACTH, which was a key design goal. No significant drug interactions have been identified. The peptide is suitable for both acute treatment (stroke recovery) and chronic use (cognitive enhancement), with no reported tolerance or dependence.

Dosing Ranges

Cognitive enhancement

Dose Range

200-600 mcg

Frequency

Once or twice daily (intranasal)

Duration

10-20 days per course

Neuroprotection / stroke recovery

Dose Range

600-1200 mcg

Frequency

Two to three times daily (intranasal)

Duration

10-14 days

Dosing information is for educational purposes only. Consult a healthcare professional before using any peptide.

Reconstitution

Preparation Details

Typical Vial Size

5 mg

Water Type

Bacteriostatic water (BAC water)

Mixing Volume

2 mL

Half-Life

~2-3 minutes (very rapid degradation; biological effects last hours due to downstream gene expression changes)

Molecular Weight

813.9 Da

Store reconstituted vial refrigerated at 2-8°C. Use within 21 days. Primarily administered intranasally. Russian pharmaceutical form is supplied as ready-to-use nasal drops (0.1% or 1% solution).

Regulatory Status

FDA Status

Not FDA approved for human use. Approved in Russia for stroke recovery, cognitive impairment, and optic nerve disease.

Legal Status

Unregulated research chemical in most countries. Prescription medication in Russia and Ukraine.

USA

Not approved

Not evaluated by FDA

EU

Not approved

Not authorized by EMA

UK

Not approved

Not licensed by MHRA

Australia

Not approved

Not evaluated by TGA

Russia

Approved

Prescription medication since 1996 for stroke recovery, cognitive impairment, optic nerve disease

Ukraine

Approved

Available as prescription nasal spray

Cited Studies

ACTH(4-10) and its synthetic analog semax: neuroprotective effects and mechanisms of action

Dolotov OV, Karpenko EA, Inozemtseva LS, Seredenina TS, Levitskaya NG, Rozyczka J, Dubynina EV, Novosadova EV, Andreeva LA, Alfeeva LY, Grivennikov IA, Myasoedov NF

Neurochemical Journal (2006)

Comprehensive analysis of Semax neuroprotective mechanisms including BDNF upregulation and neuronal survival pathways in ischemic models.

View Study →

Transcriptomic analysis of the effects of the ACTH(4-7)-PGP peptide (Semax) on gene expression in the rat brain

Dergunova LV, Filippenkov IB, Stavchansky VV, Denisova AE, Yuzhakov VV, Mozerov SA, Khvorova IA, Limborska SA, Myasoedov NF

Frontiers in Neuroscience (2020)

Genome-wide transcriptomic study revealing Semax modulation of gene expression patterns involved in neuroprotection, inflammation, and neurotransmitter signaling.

View Study →

The neuropeptide Semax affects the expression of genes related to the immune and vascular systems in the rat brain focal ischemia model

Dergunova LV, Filippenkov IB, Stavchansky VV, Limborska SA, Myasoedov NF

BMC Genomics (2014)

Demonstrated that Semax modulates immune and vascular gene networks in ischemic brain tissue, providing molecular evidence for its stroke recovery applications.

View Study →

Track Semax and more with PinnyPeptide.

Sign Up to Track